IRTA2 antibodies and methods of use

Abstract

Antibodies that specifically bind the extracellular domain of IRTA2 are disclosed herein. In one embodiment, these antibodies do not specifically bind IRTA1, IRTA3, IRTA4, or IRTA5. In one example, the antibodies are humanized antibodies. The antibodies can be conjugated to effector molecules, including detectable labels, radionucleotides, toxins and chemotherapeutic agents. The antibodies that specifically bind IRTA2 are of use to detect B cell malignancies, such as hairy cell leukemia and non-Hodgkin's lymphoma. These antibodies that specifically bind IRTA2 are also of use to treat B cell malignancies that express IRTA2, such as hairy cell leukemia and non-Hodgkin's lymphoma.

1. An isolated monoclonal antibody or an antigen-binding fragment thereof, wherein the antibody comprises
 A light chain with a L-CDR1, L-CDR2 and L-CDR3 region, and wherein L-CDR1 comprises the amino acid sequence set forth as amino acids 24 to 35 of SEQ ID NO:4, L-CDR2 comprises the amino acid sequence set forth as amino acids 51-57 of SEQ ID NO:4, and L-CDR3 comprises the amino acid sequence set forth as amino acids 90-98 of SEQ ID NO:4; 
 and wherein the antibody comprises a heavy chain with a H-CDR1, H-CDR2 and H-CDR3 region, and wherein H-CDR1 comprises the amino acid sequence set forth as amino acids 31 to 35 of SEQ ID NO:3, H-CDR2 comprises the amino acid sequence set forth as amino acids 50 to 67 of SEQ ID NO:3, and H-CDR3 comprises the amino acid sequence set forth as amino acids 100-107 of SEQ ID NO:3, 
 wherein the isolated monoclonal antibody specifically binds the amino acid sequence set forth as amino acids 287 to 565 of SEQ ID NO: 13. 
 
     
     
       2. The isolated monoclonal antibody of  claim 1 , or antigen binding fragment thereof, wherein the antibody comprises a human framework region. 
     
     
       3. The isolated monoclonal antibody of  claim 1 , or antigen binding fragment thereof, wherein the antibody comprises a murine framework region. 
     
     
       4. The isolated antigen binding fragment of the monoclonal antibody of  claim 1 . 
     
     
       5. The isolated antigen binding fragment of the antibody of  claim 2 , wherein the antigen binding fragment comprises an Fv, an Fab, or an F(ab′) 2 . 
     
     
       6. The isolated monoclonal antibody or antigen binding fragment of  claim 1 , conjugated to an effector molecule. 
     
     
       7. The isolated monoclonal antibody or antigen binding fragment of  claim 6 , wherein the effector molecule is a toxin. 
     
     
       8. The isolated monoclonal antibody or antigen binding fragment of  claim 7 , wherein the effector molecule comprises ricin A, abrin, diphtheria toxin or a subunit thereof,  Pseudomonas  exotoxin or a portion thereof, saporin, restrictocin or gelonin. 
     
     
       9. The isolated monoclonal antibody or antigen binding fragment of  claim 8 , wherein the effector molecule comprises a  Pseudomonas  exotoxin, wherein the  Pseudomonas  exotoxin comprises the amino acid sequence set forth as SEQ ID NO: 53 (PE40), SEQ ID NO: 54 (PE38), SEQ ID NO: 55 (PE38 KDEL), SEQ ID NO: 56 (PE38REDL) or SEQ ID NO: 57 (PE4E). 
     
     
       10. A composition comprising a therapeutically effective amount of the antibody of  claim 1  in a pharmaceutically acceptable carrier. 
     
     
       11. A method for detecting soluble protein comprising the amino acid sequence set forth as amino acids 287 to 565 of SEQ ID NO: 13 in a sample, comprising:
 contacting the sample with the isolated monoclonal antibody of  claim 1 , the antigen binding fragment thereof or a humanized form thereof to form an antibody protein complex; and 
 detecting the presence or absence of the complex, 
 wherein presence of the complex detects the soluble protein. 
 
     
     
       12. The method of  claim 11 , wherein the monoclonal antibody, humanized form thereof, or antigen binding fragment is labeled. 
     
     
       13. The method of  claim 12 , wherein the label is fluorescent. 
     
     
       14. The method of  claim 11 , wherein the method comprises an enzyme-linked immunosorbent assay (ELISA). 
     
     
       15. The isolated monoclonal antibody of  claim 1  or antigen binding fragment thereof, wherein a light chain variable region of the antibody comprises the amino acid sequence set forth as SEQ ID NO: 4. 
     
     
       16. The isolated monoclonal antibody of  claim 1 , or antigen binding fragment thereof, wherein a heavy chain variable region of the monoclonal antibody comprises the amino acid sequence set forth as SEQ ID NO: 3. 
     
     
       17. A hybridoma that produces the monoclonal antibody of  claim 1 .